Takeuchi Koh, Minakawa M, Otaki M, Odagiri S, Itoh K, Murakami A, Yaku H, Kitamura N
Department of Cardiac Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan.
Jpn J Physiol. 2003 Dec;53(6):411-6. doi: 10.2170/jjphysiol.53.411.
Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.
已知甲状腺功能亢进会影响多个器官的功能，并且甲状腺激素已被证实可改善衰竭心脏的心肌功能。本研究的目的是阐明甲状腺激素对长期暴露于过量甲状腺激素的大鼠模型心肌的功能和代谢影响，特别关注肌浆网Ca(2 +)-ATP酶（SERCA2）的功能。皮下注射3,5,3'-三碘-L-甲状腺原氨酸（T3）或赋形剂，持续4周（T3组和对照组[C]）。在Langendorff灌注心脏中，静脉推注毒胡萝卜素（TG）以测试SERCA2功能（C-TG和T3-TG）。测量心肌功能，如左心室舒张末压（LVDP；mmHg）、+/- dP/dt（mmHg/s）、心肌松弛时间常数（tau；ms）和耗氧量（MVO(2)；ml/min/g体重）。还通过蛋白质免疫印迹法评估SERCA2和葡萄糖转运蛋白4（GLUT4）的蛋白质水平。T3组的左心室重量与体重（LV/BW）之比显著更高。TG可使负向dP/dt和tau均显著降低。有趣的是，与正常心脏（C-TG）相比，甲状腺功能亢进组（T3-TG）中TG导致的负向dP/dt和tau的降低幅度显著更大。对照组和T3组之间SERCA2和GLUT4的蛋白质水平无显著差异。我们得出结论，长期暴露于甲状腺激素会导致心肌肥大和肌浆网Ca(2 +) ATP酶活性增强。在缺血再灌注过程中，当SERCA2功能受到抑制时，甲状腺功能亢进的心脏必须加以注意。
